Autoplatelet cartridge device

ABSTRACT

Embodiments of a platelet testing system include an analyzer console device and a blood testing cartridge configured to releasably install into the console device. The cartridge device is configured with one or more measuring chambers and one or more mixing chambers that are fluidically connected within the cartridge device that enable the mixing of saline and a blood sample to a desired dilution. Additionally, the cartridge device is further configured with a cartridge slider that provides a reagent bead to the saline and blood mixture at a desired time. As such, one or more platelet activation assays can be conducted by measuring, through cartridge electrodes of the cartridge device, the detectable changes in platelet activity within the blood and saline mixture.

TECHNICAL FIELD

This disclosure relates to systems and method for testingcharacteristics of a blood sample, and more specifically, to a cartridgesystem for characterizing platelet activity of a blood sample.

BACKGROUND

Hemostasis is the human body's response to blood vessel injury andbleeding. Hemostasis involves a coordinated effort between platelets andnumerous blood clotting proteins (or clotting factors), resulting in theformation of a blood clot and the subsequent stoppage of bleeding.

Various methods have been introduced to assess the potential ofplatelets to form an adequate clot and to determine the clot'sstability. Common laboratory tests such as thrombocyte counts or thedetermination of fibrin concentration provide information on whether thetested component is available in sufficient amount, but some of thosetests may not answer the question of whether the tested component worksproperly under physiological conditions. Other laboratory tests work onblood plasma, which may impose additional preparation steps andadditional time beyond what is preferred, for example, in thepoint-of-care context or in a surgical theater during a surgicaloperation.

Another group of tests involve assessing the potential of platelets froma blood sample to form an adequate clot. As an example, the clotfirmness (or other parameters dependent thereon) is determined over aperiod of time from the formation of the first fibrin fibers until thedissolution of the blood clot by fibrinolysis. Blood clot firmness is afunctional parameter which contributes to hemostasis in vivo, as a clotmust resist blood pressure and shear stress at the site of vascularinjury or incision. In many cases, clot firmness may result frommultiple interlinked processes including coagulation activation,thrombin formation, fibrin formation and polymerization, plateletactivation, and fibrin-platelet interaction.

To isolate and test particular functions of thrombocytes, fibrinogen,platelets, and other factors in a blood sample, reagent compounds can bemixed with the blood sample to activate or inhibit their activity in theblood sample. In some commercially available point-of-care blood testingsystems, liquid reagents are injected into a disposable plastic cupcontaining a blood sample, and the cup is then engaged by the controlconsole of the blood testing system to evaluate characteristics of thecoagulation/clotting of the blood sample. As part of the test process,the system requires manual intervention by the operator for each of theassays, for example, when pipettes are used by an operator for thedispensing and measuring of the reagents, blood, and mixed samples.Manual intervention is often inaccurate and may often result in manualerror and is, therefore, an undesirable method of assaying activity ofcomponents in a blood sample.

SUMMARY

Some embodiments of a system for testing characteristics of a bloodsample (which, as used herein, should be understood to include blood orderivatives of blood such as plasma) can include a cartridge configuredto mate with a control console and receive a blood sample for apoint-of-care whole blood coagulation analysis. In particularcircumstances, the cartridge is configured to interact with the controlconsole so as to perform a number of automated transport and testingoperations on portions of the blood sample so as to provide reliable andprompt results indicative of a patient's blood characteristics at thepoint-of-care. For example, the system can serve as an automated systemfor providing detailed and prompt results of blood coagulationcharacteristics in response to receiving a cartridge (and blood sampleat the cartridge) and an indication from an operator to begin theautomated testing process.

In some embodiments, the system includes a reusable analyzer console andone or more single-use cartridge components configured to mate with theconsole. In one example, to operate the system, a user inserts thecartridge into the analyzer console and, when prompted by the analyzerconsole, inserts a blood collection tube (containing a whole bloodsample) into a receiver portion of the cartridge. Thereafter, theanalyzer console automatically performs (without requiring further userinteraction with the cartridge or the blood sample) the testing, anddisplays the results on a graphical display using qualitative graphicalrepresentations and quantitative parameters. In this particular example,no manual pipetting, mixing, or handling of reagents by the user isneeded. In some embodiments, three or more assays are automaticallyperformed on the blood sample using a single cartridge device. Suchassays provide information on the whole kinetics of hemostasis, such asclotting time, clot formation, clot stability, and lysis; moreover, suchinformation can be promptly output from a user interface of the systemto provide reliable and prompt results indicative of a patient's bloodcharacteristics at the point-of-care (e.g., while the patient is in asurgical room undergoing surgery).

Particular embodiments described herein include a cartridge for use witha blood testing console. The cartridge may include a blood samplereceiver configured to receive a blood sample to be tested. Thecartridge may additionally include a hermetically sealed container ofsaline. The cartridge may be configured to mix a portion of the bloodsample with the saline to achieve a desired dilution of a portion of theblood sample. To do so, the cartridge may include one or more fluidprocessing and testing paths. In various embodiments, the cartridgeincludes one or more valves and vents that enable control over the fluidflow through the fluid processing and testing paths. Namely, each fluidprocessing and testing path enables fluid flow into one or moremeasuring chambers that are each is configured to provide fluid througha valve to a corresponding mixing chamber. As such, a desired volume ofblood or saline can be precisely measured by the measuring chamber andsubsequently provided to the mixing chamber to achieve the desireddilution.

In various embodiments described herein, the cartridge is furtherconfigured to receive one or more reagents that are to be provided tothe mixing solution within the mixing chamber. The reagent may be areagent bead, and in various embodiments, the reagent is composed of aplatelet activator. The cartridge may include a cartridge slidersituated within the cartridge that is configured to receive the reagent,hold the reagent until a particular time, and provide the reagent to theappropriate mixing chamber. Additionally, in various embodimentsdescribed herein, the cartridge is configured to capture a measurementof the blood and saline mixture in the mixing chamber. Namely, thecartridge may include one or more cartridge electrodes, each positionedwithin the cartridge to capture an impedance measurement of the bloodand saline mixture while the solution resides within the mixing chamber.In various embodiments, the measurement is captured after one or morereagents are provided to the mixing solution within the mixing chamber.As such, an identification of the platelet activity within the bloodsample can be determined through the captured measurement.

Some or all of the embodiments described herein may provide one or moreof the following advantages. First, some embodiments of the system areconfigured to be automated so that user interactions with the system areminimized. As a result, human resources can be diverted and utilizedwith greater efficiency. The reduction of user interactions can alsoreduce the chances for manual operator errors, such as measuringinaccuracies, reagent mixing errors, and the like. Accordingly, moreaccurate results may be attained in some circumstances.

Second, in some embodiments, the cartridge includes multiple fluidchannels that are each individually controllable so that multipledifferent assays can be performed from a single supply of a bloodsample. For example, each fluid channel between a measuring chamber anda mixing chamber includes a dedicated valve that is controllable by theanalyzer console so that the blood flow is individually controllable.This feature enables the system to automatically perform sophisticatedassay processes.

Third, in some embodiments, the cartridge includes chambers that aredesigned to accurately measure solution volumes, such that when bloodand saline are mixed, a desired ratio of blood and saline can beaccurately achieved. This enables testing reproducibility that is oftendifficult to achieve when manual intervention is required (e.g.,pipetting).

Fourth, in some embodiments, the analyzer console can be configured toperform a number of quality-control operations/confirmations so as toensure the blood test results are not compromised. For example, theanalyzer console can be configured to verify the blood testing cartridgeis heated to a target temperature (e.g., about 37° C.) prior to theblood sample being distributed to testing chambers of the cartridge.Because temperature of the blood sample can affect the coagulationcharacteristics in some circumstances, the accuracy of the results maybe enhanced as a result of such temperature-controloperations/confirmations.

Fifth, in particular embodiments of the cartridge device, the geometryof the fluid flow paths through the fluid channels of the cartridge areconfigured to reduce the potential for disturbing the fluid (e.g.,causing bubble formation, etc.), and/or damaging the fluid, in a mannerthat may negatively impact the accuracy of the test results. Furtheradvantages associated with the systems provided herein are alsoenvisioned, as will be evident from the following disclosure.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

BRIEF DESCRIPTIONS OF THE DRAWINGS

The disclosed embodiments have other advantages and features which willbe more readily apparent from the following detailed description of theinvention and the appended claims, when taken in conjunction with theaccompanying drawings, in which:

Figure (FIGS.) 1A, 1B, 2, and 3 are perspective illustrations depictingthe components and use of an example system, in accordance with anembodiment.

FIG. 4 is an exploded view of the example autoplatelet cartridge of thesystem of FIGS. 1A, 1B, 2, and 3, in accordance with an embodiment.

FIG. 5A is a left side view of the autoplatelet cartridge body, inaccordance with an embodiment.

FIG. 5B is a right side view of the autoplatelet cartridge body, inaccordance with an embodiment.

FIG. 6A is a view of the internal side of the left cover, in accordancewith an embodiment.

FIG. 6B-6D depict perspective views of the left cover, in accordancewith an embodiment.

FIG. 7A is a view of the internal side of the right cover, in accordancewith an embodiment.

FIG. 7B is a view of the external side of the right cover, in accordancewith an embodiment.

FIG. 7C depicts a top view of the right cover, in accordance with anembodiment.

FIG. 8A depicts a top down view of the cartridge body, in accordancewith an embodiment.

FIG. 8B depicts a cutaway of the cartridge body including the bead dropinlet, in accordance with an embodiment.

FIG. 8C depicts a side cutaway of the cartridge body that illustratesthe bead drop inlet in relation to a mixing chamber, in accordance withan embodiment.

FIG. 9A depicts a top down view of the cartridge electrodes within thecartridge body, in accordance with an embodiment.

FIG. 9B-9E each depicts a view of a cartridge electrode, in accordancewith an embodiment

FIG. 10A depicts a cartridge slider, in accordance with an embodiment.

FIG. 10B depicts a side view of the cartridge slider, in accordance withan embodiment.

FIG. 11A-11B each illustrates a cutaway view of an assembledautoplatelet cartridge as a reagent bead enters into a mixing chamber,in accordance with an embodiment.

FIG. 12A-C illustrates a flow process of testing platelet behavior usingthe autoplatelet cartridge, in accordance with an embodiment

FIG. 13A-B illustrate an overview of the analyzer console, in accordancewith an embodiment.

DETAILED DESCRIPTION

The figures and the following description relate to preferredembodiments by way of illustration only. It should be noted that fromthe following discussion, alternative embodiments of the structuresdisclosed herein will be readily recognized as viable alternatives thatmay be employed without departing from the principles of what isclaimed.

Reference will now be made in detail to several embodiments, examples ofwhich are illustrated in the accompanying figures. It is noted thatwherever practicable similar or like reference numbers may be used inthe figures and may indicate similar or like functionality. The figuresdepict embodiments of the disclosed system for purposes of illustrationonly. One skilled in the art will readily recognize from the followingdescription that alternative embodiments of the structures illustratedherein may be employed without departing from the principles describedherein.

The figures use like reference numerals to identify like elements. Aletter after a reference numeral, such as “425 a,” indicates that thetext refers specifically to the element having that particular referencenumeral. A reference numeral in the text with multiple letters, such as“425 a-c” refers to any individual or combination of the elements in thefigures bearing that reference numeral.

Overview Configuration

Referring to FIGS. 1A-3, some embodiments of a blood testing system 100include an analyzer console 140 and one or more autoplatelet cartridges120 configured to releasably mate with analyzer console 140. In thisembodiment, the blood testing system 100 is configured to determine anumber of blood coagulation characteristics of a blood sample input intothe autoplatelet cartridge 120. For example, the autoplatelet cartridge120 can be configured as a single-use cartridge that includes a bloodsample well 122 for mating with a blood sample reservoir 10 (e.g., avacutainer sample tube supplied by Becton, Dickinson & Company ofFranklin Lakes, N.J., or another blood reservoir structure). In somecases, an adapter may be used to couple other types of blood samplereservoirs 10 with the cartridge 120 (e.g., tubing may be used throughwhich blood can be injected into the cartridge 120, and the like). Thesystem 100 can be used as a whole blood coagulation analysis system thatis particularly advantageous at a point-of-care site (e.g., in asurgical theater while a patient is undergoing or preparing for surgery,or the like). Additionally, system 100 can be used as a whole bloodcoagulation analysis system in a laboratory setting.

The analyzer console 140 includes a user interface 142 (with touchscreendisplay in this embodiment) and a main chassis 144. The user interfacedisplay 142 can be configured to output one or more graphical results143 from the blood testing assays performed via the autoplateletcartridge 120 and analyzer console 140 (e.g., one or more plots, such asthose sometimes refer to as a TEMogram, numeric data or measurements, ora combination thereof). In some embodiments, the user interface display142 is rigidly attached to the analyzer console 140. In particularembodiments, the user interface display 142 is pivotable and/or isotherwise positionally adjustable in relation to the main chassis 144. Amain power switch 148 can be located at a convenient but protectedlocation on the main chassis 144.

In the depicted embodiment, the touchscreen display 142 is configured toreceive user input and to display output information to the user. Forexample, the user can enter information to the system 100 by makingselections of various soft-buttons that may be displayed on thetouchscreen display 142 at times during the beginning, middle, and endof the testing process. In some embodiments, other selections such as,but not limited to, soft keyboard entries can be provided viatouchscreen display 142. In some embodiments, data entry can beperformed additionally or alternatively by voice entry. In otherembodiments, the user interface may include other peripheral devices canbe included (e.g., a mouse, a keyboard, an additional display device,and the like) as part of the system 100. In some embodiments, a computerdata network (e.g., intranet, internet, LAN, etc.) may be used to allowfor remote devices to receive and/or input information from the system100. For example, in some embodiments one or more remote displays can beutilized via network connections. In the depicted embodiment, the system100 also includes an external barcode reader. The external barcodereader can facilitate convenient one-dimensional or two-dimensionalbarcode entry of data such as, but not limited to, blood sample data,user identification, patient identification, normal values, and thelike. Alternatively or additionally, the system 100 can be equipped witha reader configured to read near-field communication tags, RFID tags, orthe like.

In the depicted embodiment, the main chassis 144 houses various internalsub-systems (as described further below), includes various electronicconnection receptacles (not shown), and includes a cartridge port 150.The various electronic connection receptacles can include network anddevice connectors such as, but not limited to, one or more USB ports,Ethernet ports (e.g., RJ45), VGA connectors, Sub-D9 connectors (RS232),and the like. Such connection receptacles can be located on the rear ofthe main chassis 144, or at other convenient locations on the mainchassis 144. For example, in some embodiments one or more USB ports maybe located on or near the front of the main chassis 144. A USB port, solocated, may provide user convenience for recording data onto a memorystick, for example. In some embodiments, the system 100 is configured tooperate using wireless communication modalities such as, but not limitedto, Wi-Fi, Bluetooth, NFC, RF, IR, and the like.

Still referring to FIGS. 1A-3, the cartridge port 150 can be located ata readily accessible location on the main chassis 144. In the depictedembodiment, the cartridge port 150 is located on the front of the mainchassis 144 so that it is conveniently accessible by a user in apoint-of-care site. The cartridge port 150 defines an opening andinternal space that is shaped complementarily to the outer dimensions ofthe autoplatelet cartridge 120. To insert the autoplatelet cartridge 120into the cartridge port 150, the user can grasp the end of theautoplatelet cartridge 120 that includes the blood sample receiver 122and slidingly insert the opposite end (leading end) into the cartridgeport 150. The sliding insertion can continue until a hard-stop isreached that defines the fully inserted position. In the fully insertedposition, a trailing end portion (including the blood sample receiver122 in this embodiment) of the autoplatelet cartridge 120 remainsexterior to the main chassis 144. The portion of the autoplateletcartridge 120 that is received into the cartridge port 150 can includeouter surface features (such as a tapered angle a rear end portion shownin FIG. 1B) that mate with at least one internal interface elementinside the console 140 to ensure correct positioning of the autoplateletcartridge 120. As such, at least the blood sample receiver 122 remainsexterior to the main chassis 144 throughout the duration of the bloodsample testing. In this configuration, the blood sample receiver 122serves as a blood sample well that is accessible so that the bloodsample reservoir 10 can be inserted into the receiver 122 while theautoplatelet cartridge 120 is mated with the console 140 in the fullyinserted position. In some embodiments, the cartridge port 150 and themain chassis 144 are configured so that the exposed portion of theautoplatelet cartridge 120 is protected from inadvertent contact. Asdescribed further below, an internal sensor (e.g., a microswitch, anoptical sensor, etc.) can detect when the autoplatelet cartridge 120 hasbeen fully inserted into the main chassis 144.

When the analyzer console 140 has detected that the autoplateletcartridge 120 has been fully inserted, in some embodiments the analyzerconsole 140 initiates one or more of the following actions. An internalcartridge clamping mechanism that includes positioning pins can beactivated to accurately position and releasably retain the autoplateletcartridge 120 in the fully inserted position. One or more cartridgeheating elements can be activated to warm the cartridge 120. Thetemperature of the autoplatelet cartridge 120 can be monitored. Abarcode on the leading end of the autoplatelet cartridge 120 can be readand the barcode data can be stored in memory of the analyzer console140. One or more blood detection sensors can inspect the autoplateletcartridge 120 for the presence of blood. The platelet activitymeasurement system can be engaged with the autoplatelet cartridge 120 tobegin testing of the platelet. The cartridge 120 can be leak testedusing vacuum or air pressure delivered by the analyzer console 140. Forexample, a pressure/vacuum decay test can be performed. In someembodiments, other actions can be additionally or alternativelyactivated when the analyzer console 140 has detected that theautoplatelet cartridge 120 has been fully inserted. After the completionof such actions, in some embodiments an indication of the results of theactions may be displayed on the touchscreen display 142 (e.g., pass orfail). If the analyzer console 140 determines that the actions werecompleted successfully, a prompt can be provided on the touchscreendisplay 142 that informs the user that the system 100 is ready toreceive the blood sample reservoir 10. Further discussion regarding theanalyzer console 140 of the system 100 is described below in referenceto FIG. 13A-B.

Briefly, in some embodiments a user can operate the depicted system 100embodiment as follows. First, the user can insert the autoplateletcartridge 120 into the cartridge port 150 so that the autoplateletcartridge 120 is placed into the fully inserted position. Completion ofthat step will automatically initiate a series of operations by thesystem 100 as described below. Upon successful completion of suchoperations, a notification that the blood collection tube 10 can beinserted into the sample well 122 will be displayed on the touchscreendisplay 142. After the user has mated the blood collection tube 10 intothe sample well 122, the user initiates testing by pressing a “start”button (or the like) on the touchscreen display 142. At least the bloodmeasuring, reagent mixing, and testing is performed automatically by thesystem 100 thereafter (e.g., without requiring manual intervention fromthe user in this embodiment). When the testing is completed, the resultsare displayed on the touchscreen display 142 in the form of qualitativegraphical representations and quantitative parameters (e.g., as depictedin FIG. 1A). Also, when the testing is completed, the autoplateletcartridge 120 can be removed from the analyzer console 140. Theautoplatelet cartridge 120 may be reused or discarded.

Alternately, in some embodiments the blood collection tube 10 can beinserted into the sample well 122 of the autoplatelet cartridge 120prior to insertion of the autoplatelet cartridge 120 into the cartridgeport 150. In such circumstances, the blood from the collection tube 10may not advance into the fluid channels of the autoplatelet cartridge120 until after the analyzer console 140 acts upon the autoplateletcartridge 120 (again, as described below). With the blood collectiontube 10 being pre-coupled with the autoplatelet cartridge 120, thecombination of the blood collection tube 10 and the autoplateletcartridge 120 can then be inserted into the cartridge port 150.

Autoplatelet Cartridge Device

Reference is now made to FIG. 4, which depicts an exploded view of asample autoplatelet cartridge 120 of the system 100 of FIGS. 1A, 1B, 2,and 3, in accordance with an embodiment. The autoplatelet cartridge 120includes a cartridge body 405, a left cover 410, a right cover 415, anampoule 408, a cartridge slider 420, and one or more cartridgeelectrodes 425 a-c. In various embodiments, the autoplatelet cartridge120 may further include one or more reagent beads. The reagent beads areincluded in the autoplatelet cartridge 120 for activating the plateletsin a blood sample, thereby enabling the measurement of platelet activityin the blood sample.

The cartridge body 405 includes the aforementioned sample well 122 whichis situated on one end of the cartridge body 405 as well as multipleledges 430 a-b that are each configured to be in contact with theampoule 408 of the autoplatelet cartridge 120. The cartridge body 405may further include a cavity 450 on a top surface of the cartridge body405 as well as multiple slots 440 adjacent to the cavity 450. Each slot440 may be located on the left wall of the cartridge body 405.Additional embodiments of the construction of an autoplatelet cartridge120 are also envisioned. Each of the elements of the cartridge body 405is further described below in regards to the other components of theautoplatelet cartridge 120.

The left cover 410 is affixed to left side of the cartridge body 405,and the right cover 415 is affixed to the right side of the cartridgebody 405. As such, the left and right covers 410 and 415 enclosechambers and flow channels of the cartridge body 405 to define fluidflow paths as described further below.

The ampoule 408 of the autoplatelet cartridge 120 may include a firstend 435 a and a second end 435 b. As depicted in FIG. 4, the ampoule 408is cylindrical in shape with hemispherical ends 435 a-b. In variousembodiments, the ampoule 408 may take on any other number of formfactors. In various embodiments, the ampoule 408 is a closed vessel suchas a hermetically sealed container and stores a fluid. For example, thefluid may be a saline solution. More specifically, the fluid may be anormal saline solution. Additionally, the ampoule 408 may be constructedfrom an easily rupturable material such as glass or aluminum such thatan external force imparted on a wall of the ampoule 408 would cause theampoule 408 to rupture and release the stored fluid. In otherembodiments, there is a valve or other release mechanism associated withthe ampoule 408. In various embodiments, the ampoule 408 is configuredto sit within a chamber of the cartridge body 405 when the autoplateletcartridge 120 is fully assembled. For example, the first end 435 a ofthe ampoule 408 sits in contact with a top surface of a first ledge 430a. Similarly, the second end 435 b of the ampoule 408 sits in contactwith a top surface of a second ledge 430 b. The ampoule 408 can begeometrically configured such that when sitting in contact with themultiple ledges 430 a-b within the chamber of the cartridge body 405,the ampoule 408 does not translationally displace relative to thecartridge body 405 due to being in contact with the ledges 430 a-b andthe walls of the chamber.

The cartridge electrodes 425 a-c are each configured to determineplatelet function (e.g., platelet aggregation) by measuring impedanceand/or changes in impedance in a blood sample. When the autoplateletcartridge 120 is assembled, each cartridge electrode 425 a-c resideswithin a slot 440 in the cartridge body. As such, the cartridgeelectrode 425 a-c can be used to take a measurement of a solution withinthe autoplatelet cartridge 120. In various embodiments, the cartridgeelectrodes 425 a-c are geometrically designed to block off the slot 440on the left wall of the cartridge body 405. Namely, the cartridgeelectrode 425 a-c, when assembled with the cartridge body 405, preventssubstances from entering into the cartridge body 405 through the slot440.

The cartridge slider 420 is configured to slide within the cavity 450 ofthe cartridge body 405. When the autoplatelet cartridge 120 isassembled, the cartridge slider 420 is situated within the cavity 450and above the cartridge electrodes 425 a-c. Namely, the cartridge slider420 longitudinally translates along the cavity 450 to achieve differentpositions. For example, in a first position, one or more reagent beadscan be loaded into the autoplatelet cartridge 120. In a second position,one or more reagent beads can be dropped into a solution mixture suchthat an impedance measurement of the solution mixture can be taken by acartridge electrode 425 a-c. In various embodiments, the cartridgeslider 420, when in the first position, is at a position in the cavity450 that is most distal relative to the sample well 122. Therefore, thecartridge slider 420 is located more proximal to the sample well 122 inthe second position relative to the first position.

Cartridge Body

Reference is now made to FIG. 5A and FIG. 5B, which each depict a sideview of the cartridge body 405, in accordance with an embodiment.Namely, FIG. 5A depicts a left side view of the cartridge body 405whereas FIG. 5B depicts a right side view of the cartridge body 405. Theelements of the cartridge body 405 will be discussed in reference toboth the left side and right side view.

Referring to the left side view of the cartridge body 405 in FIG. 5A,the cartridge body 405 includes various valve seats 510, 515, 520 a-c,and 525, an input pressure port 530, a vacuum pressure port 535, one ormore measuring chambers 518 a-c, one or more mixing chambers 519 a-c, avent port 540, a coupling point 598, and an ampoule access port 545.Referring to the right side view of the cartridge body 405 in FIG. 5B,the cartridge body 405 further includes various fluid channels 560, 562,564, 566, 568, 570, 572, and 580 a-c, an ampoule chamber 550, couplingpoints 592 and 594, and waste chamber 590. Additionally, the cartridgebody 405 includes multiple ducts (511, 512, 516, 517, 521 a-c, 522 a-c,523 a-c, 524) that run transversely (e.g., from the left side to theright side and vice versa) through the cartridge body 405, the ductsfluidically connecting the fluid channels of the cartridge body 405.

In various embodiments, each of the valve seats 510, 515, 520 a-c, and525 in the cartridge body 405 are located on the left side of thecartridge body 405. A valve seat may be an indentation in the side ofthe cartridge body 405. Each valve seat 510, 515, 520 a-c, and 525 isconfigured to receive and couple with a valve structure that is locatedon the left cover 410. When coupled with a valve structure, the valveseat 510, 515, 520 a-c, and 525 is closed and prevents fluid flowthrough corresponding fluid channels. When not in contact with areciprocal valve structure, the valve seat 510, 515, 520 a-c, and 525 isopen and allows fluid flow through the corresponding duct and fluidchannel. Further discussion regarding the opening/closing of valve seats510, 515, 520 a-c, and 525 by a corresponding valve structure on theleft cover 410 is further discussed in regards to FIG. 6. In variousembodiments, the valve seats 510, 515, 520 a-c, and 525 are interspersedwithin the path of the various fluid channels so that the fluid flow canbe controlled by a valve structure according to predefined schemes.

Referring to the specific valve seats 510, 515, 520 a-c, and 525 in thedepicted embodiment in FIGS. 5A and 5B, valve seat 510 controls thefluid flow that originates from a blood sample reservoir 10 located inthe blood sample receiver 122. Namely, the blood sample flows throughfluid channel 562 to duct 511 (see FIG. 5B) that is connected to valveseat 510 (see FIG. 5A). Therefore, when valve seat 510 is open, bloodcan flow from fluid channel 562, through duct 511, through open valveseat 510, through duct 512, and into fluid channel 564. Valve seat 515controls fluid flow between ampoule chamber 550 and fluid channel 560.Specifically, when valve seat 515 is open, fluid (e.g., saline) from theampoule chamber 550 can flow through duct 516, through open valve seat515, through duct 517, and into fluid channel 560. Valve seat 520 a-ccontrols the fluid flow between the respective measuring chamber 518 a-cand fluid channel 580 a-c. Specifically, when valve seat 520 a is open,fluid from the measuring chamber 518 a flows through duct 522 a into thecorresponding fluid channel 580 a. Similarly, when valve seat 520 b isopen, fluid from the measuring chamber 518 b flows through duct 522 binto the corresponding fluid channel 580 b. Also, when valve seat 520 cis open, fluid from the measuring chamber 518 c flows through duct 522 cinto the corresponding fluid channel 580 c. Fluid in fluid channel 580a-c can flow through a corresponding duct 523 a-c that is fluidicallyconnected to each mixing chamber 519 a-c. Valve seat 525 controls fluidflow from fluid channel 570 to waste chamber 590. Specifically, whenvalve seat 525 is open, fluid flows from the fluid channel 570, throughduct 524, through open valve seat 525 and into waste chamber 590.

The cartridge body 405 contains one or more measuring chambers 518 a-c.As depicted in FIG. 5A, there are three total measuring chambers 518a-c; however, in other embodiments there may be additional or fewermeasuring chambers 518 a-c. Each measuring chamber 518 a-c may have adefined volume (e.g., 150 μL), such that when the measuring chamber 518a-c is full of a particular fluid, the volume of that fluid is preciseor nearly precise to the defined volume. Each measuring chamber 518 a-cis in fluid connection with a fluid channel. For example, measuringchamber 518 a receives fluid from fluid channel 564 through a duct 526a. Measuring chamber 518 b receives fluid from fluid channel 566 througha duct 526 b. Measuring chamber 518 c receives fluid from fluid channel568 through a duct 526 c.

In various embodiments, the fluid in a measuring chamber 518 a-c canexit in one of two different ways. In one way, as previously described,the fluid output of each measuring chamber 518 a-c is controlled by avalve seat 520 a-c that outputs through duct 522 and into correspondingfluid channel 580. In a second way, the fluid output of each measuringchamber 518 a-c occurs through a corresponding duct 521 a-c. Each duct521 a-c is fluidically connected with a corresponding fluid channel 566,568, and 570. In various embodiments, each duct 521 a-c is located atthe top of each measuring chamber 518 a-c such that fluid flows into theduct if the measuring chamber 518 a-c is at maximum capacity. Therefore,altogether, the measuring chambers 518 a-c are fluidically connected toone another through fluid channels 566 and 568. Namely, the fluid frommeasuring chamber 518 a can flow through fluid channel 566 intomeasuring chamber 518 b which can subsequently flow through fluidchannel 568 into measuring chamber 518 c.

The cartridge body 405 also contains one or more mixing chambers 519a-c, where each mixing chamber 519 a-c is fluidically connected to apreviously described measuring chamber 518 a-c. In various embodiments,a mixing chamber 519 a-c receives and mixes two different fluids (e.g.,saline and blood). The mixing chamber 519 a-c may each include a mixingdevice (e.g., a magnetic stir bar). In one scenario, the mixing chambers519 a-c may each extend to the bottom of the cartridge body 405 suchthat a magnetic field can be applied by the analyzer console 140 to thebottom of the cartridge body 405 to actuate the mixing devices locatedwithin the mixing chamber 519 a-c.

In various embodiments, the volume of the mixing chamber 519 a-c is atleast twice the volume of the measuring chamber 518 a-c. This enablesthe mixing of equal volumes of two different fluids that are eachinitially measured in the measuring chamber 518 a-c. Additionally, eachmixing chamber 519 a-c is configured to receive a cartridge electrode425 a-c such that at least a portion of each cartridge electrode 425 a-ccan be exposed to a mixing solution within a mixing chamber 519 a-c.

Input pressure port 530 is a pressure application port where a source ofpressure can be applied. Namely, when a positive source of pressure isapplied at input pressure port 530, and when the vents and valves of thecartridge 120 are in the proper configuration, fluid can be forced toflow from the measuring chambers 518 a-c into the mixing chambers 519a-c. As depicted in FIGS. 5A and 5B, the input pressure port 530 is influid communication with the fluid channel 570. The process of applyinga positive pressure at the input pressure port 530 is further describedbelow.

Vacuum pressure port 535 is a vacuum application port where a negativesource of pressure can be applied. Namely, when a source of vacuum isapplied at the vacuum pressure port 535, and when the vents and valvesof the autoplatelet cartridge 120 are in the proper configuration, fluidcan be drawn into each of the measuring chambers 518 a-c as describedabove. As depicted in FIGS. 5A and 5B, the vacuum pressure port 535 isin fluid communication with the waste chamber 590 through fluid channel572. The process of applying the negative pressure at the vacuumpressure port 535 is further described below.

The cartridge body 405 may also include an ampoule chamber 550 that isconfigured to house the ampoule 408 that includes a fluid (e.g.,saline). As previously described, the ampoule rests on the ledges 430a-b within the ampoule chamber 550. The cartridge body 405 also includesan ampoule access port 545. In various embodiments, the ampoule 408within the ampoule chamber 550 receives an external force through theampoule access port 545. The external force may comprise a physicalforce input provided by a structure that passes through the ampouleaccess port 545. Alternatively or in addition, the external force maycomprise non-contact force such as the provided by an ultrasoundapplication. This may cause the ampoule 408 to release the fluid withinthe ampoule 408 into the ampoule chamber 550. As such, the fluid in theampoule chamber 550 can exit through duct 516, through open valve seat515, and through duct 517 into fluid channel 560. In variousembodiments, the cartridge body 405 may include a vent port 540 withinthe ampoule chamber 550. The opening and closing of the vent port 540can be controlled by the analyzer console 140 in order to ensure thatfluid can appropriately flow through the fluid channels. Namely, whenfluid is exiting the ampoule chamber 550 through open vent 515, the ventport 540 is opened to provide proper venting into the ampoule chamber550.

The cartridge body 405 also includes coupling points 592 and 594 on theright side of the cartridge body 405 that couple with the right cover415. Similarly, the cartridge body 405 may include coupling point 598 onthe left side of the cartridge body 405 that couples with the left cover410.

Cartridge Covers

FIG. 6A is a view of the internal side of the left cover 410, inaccordance with an embodiment. The left cover includes multiple valvestructures 605 a-f, vent opening 615, one or more divots 612 a-c,ampoule opening 635, and one or more pressure openings 620. Furtherreference will be made to FIG. 6B-6D which depict perspective views ofthe left cover 410, in accordance with an embodiment. More specifically,FIG. 6B illustrates a view of section H-H as depicted in FIG. 6A. FIG.6C depicts detail J of FIG. 6B. FIG. 6D depicts a top down view of theleft cover 410.

The left cover 410 includes a vent opening 615 that substantially alignswith the vent port 540 on the left side of the cartridge body 405. Assuch, the vent port 540 is open to the external environment whichenables it to appropriately vent the ampoule chamber 550. The pressureopenings 620 on the left cover 410 are positioned to substantially alignwith input pressure port 530 and vacuum pressure port 535, respectively.Therefore, the analyzer console 140 can access each port through thepressure openings 620 and apply a positive or negative pressure asneeded. Similarly, the ampoule opening 635 is substantially aligned withthe ampoule access port 545 on the left side of the cartridge body 405.Therefore, the analyzer console 140 can provide an external forcethrough the ampoule opening 635 in order to release the fluid of theampoule 408 within the cartridge body 405.

The left cover 410 also includes one or more divots 612 a-c that arelocated on the underside of an overhang of the left cover 410. Referringto FIG. 6B, the overhang 630 of the left cover 410 extends perpendicularfrom the vertical portion of the left cover 410. Each of the divots 612a-c may be configured to be in contact with one or more structures onthe cartridge slider 420 that is situated underneath the overhang 630 ofthe left cover 410. As an example, a divot 612 a-c is an indentation inthe overhang 630 of the left cover 410. The interface between the divot612 a-c and the structures of the cartridge slider 420 is described infurther detail below in regards to FIG. 10.

The multiple valve structures 605 a-f are located at various locationsof the left cover 410 to correspond to the locations of the valve seats510, 515, 520, and 525 on the left side of the cartridge body 405. Aspreviously stated, each valve structure 605 a-f is configured to contactor couple with a corresponding valve seat 510, 515, 520 a-c, and 525.Therefore, when a valve structure 605 a-f is in contact with acorresponding valve seat 510, 515, 520 a-c, and 525, fluid flow throughcorresponding fluid channels is blocked.

Reference is now made to FIG. 6C that provides, in more detail, thestructure of a valve structure 605 d. In various embodiments, each valvestructure 605 a-f includes an elastomeric member 610 that is responsiblefor contacting a corresponding valve seat 510, 515, 520 a-c, and 525. Asdepicted in FIG. 6C, the elastomeric membrane 610 is a hemisphericstructure.

In various embodiments, the elastomeric member 610 of each valvestructure 605 a-f is deformable upon application of pressure on theexternal side of the left cover 410. Application of external pressure onthe elastomeric member 610 of the valve structure 605 a-f causes theelastomeric member 610 to deform inward (e.g., in FIG. 6C, towards theleft), thereby contacting a corresponding valve seat 510, 515, 520, and525 and fluidically sealing a corresponding fluid channel.

In various embodiments, the application of external pressure on a valvestructure 605 a-f can be actuated by the analyzer console 140. Forexample, the analyzer console 140 may utilize valve actuators thatinclude a coupled pin. The coupled pin can extend to make contact withand to distend elastomeric material 610 of valve structures 605 a-f suchthat the elastomeric material 610 makes contact with a valve seat 510,515, 520 a-c, and 525 within the cartridge body 405. In otherembodiments, a valve actuator may comprise a solenoid that includesinternal springs that cause the valve actuators to be normally extended.Accordingly, such normally closed solenoids will close the valvestructures/seats of the cartridge body 405 as a default configuration.

Referring now to FIG. 6D, the overhang 630 of the left cover 410 mayinclude three overhang openings 625 a-c. Each overhang opening 625 a-cis configured to receive reagent beads for the testing of plateletactivity. For example, the overhang opening 625 a-c may be circular orovoid in shape, the overhang opening 625 a-c being larger than thediameter of a reagent bead, such that the reagent bead can be providedto the underlying cartridge slider 420 and into the cartridge body 405.Additionally, the overhang 630 includes an indentation 640. Theindentation 640, in part, allows access to the cartridge slider 420 thatsits underneath the overhang 630.

Reference is now made to FIG. 7A, which depicts a view of the internalside of the right cover 415, in accordance with an embodiment. FIG. 7Bis a view of the external side of the right cover 415, in accordancewith an embodiment. The right cover 415 includes a slider access port710 and one or more elevated structures 705 on the internal side of theright cover 415. Additionally, the right cover 415 includes one or morefluid detection locations 730 a-b as well as one or more coupling points720 and 725.

The slider access port 710 enables access to the side of the cartridgeslider 420. In various embodiments, the slider access port 710 isrectangular in shape, thereby allowing access to a horizontal portion ofthe cartridge slider 420. The right cover 415 may also include one ormore coupling points 720 and 725 that are positioned to substantiallyalign with coupling points 592 and 594 of the right side of thecartridge body 405. In various embodiments, the right cover 415 alsoincludes one or more elevated structures 705 that may be designed tocorrespond to the various fluid channels 560, 562, 564, 566, 568, 570,572, and 580 a-c of the cartridge body 405. Namely, when fluid isflowing through the fluid channels, the elevated structures 705 of theright cover 415 assist in preventing fluid from escaping the fluidchannels into other portions of the cartridge body 405.

The fluid detection locations 730 a-b are positioned on the right cover415 to detect the presence of fluid in particular locations within thecartridge body 405. As will be described further below, the fluiddetection location 730 a-b are designated locations on the cartridgebody 405 at which sensors of the analyzer console 140 interface with theautoplatelet cartridge 120. In some embodiments, the sensors applied tothe fluid detection location 730 a-b are optical sensors, such as IR(infrared) sensors. In some embodiments, the fluid detection locations730 a-b are polished areas that have enhanced transparency and opticalclarity. As such, the right cover 415 is configured so that the opticalsensors of the analyzer console 140 can readily detect the presence orabsence of fluid at the fluid detection locations 730 a-b. As anexample, fluid detection location 730 a detects fluid in fluid channel564 whereas fluid detection location 730 b detects fluid in fluidchannel 570 before the fluid enters into waste chamber 590.

Referring now to FIG. 7C, it depicts a top view of the right cover 415,in accordance with an embodiment. The right cover 415 may include anoverhang 715 (similar to overhang 630 on the left cover 410) that islocated at the top of the right cover 415 and extends perpendicular tothe vertical portion of the right cover 415. Additionally, the overhang715 may include an indentation 740 that is designed to align with theindentation 640 of the overhang 630 of the left cover 415. Therefore,when taken together, the two indentations 640 and 740 form an openingthat enables access to the cartridge slider 420 located underneath theoverhangs 630 and 715 of the left cover 410 and right cover 415,respectively.

Mixing Chamber of the Cartridge Body

FIG. 8A depicts a top down view of the cartridge body 405, in accordancewith an embodiment. As previously described, the cartridge body 405includes multiple openings 440 that are located along the left side ofthe cartridge body 405 and above the mixing chambers 519 a-c.Additionally, the cartridge body 405 includes bead drop inlets 805 a-clocated within the mixing chambers 519 a-c.

In various embodiments, the multiple slots 440 along the side of thecartridge body 405 extend from the top of the cartridge body 405 down acertain distance along the cartridge body 405. In various embodiments,the multiple slots 440 extend downward a distance that is less than halfof the height of the cartridge body 405. As depicted in FIG. 8A, mixingchambers 519 a-c are cylindrically shaped. As previously described, eachmixing chamber 519 a-c may include a mixing device (e.g., a magneticstirrer) that facilitates the mixing of fluid within the mixing chamber519 a-c. In various embodiments, the bead drop inlets 805 a-c arelocated along the cartridge body 405 such that a reagent bead can beprovided through the bead drop inlet 805 a-c to a mixing chamber 519a-c. As an example, the bead drop inlets 805 a-c are substantiallyaligned with the overhang openings 625 a-c of the left cover 410. Thus,a reagent bead provided to the autoplatelet cartridge 120 through theoverhang openings 625 a-c can directly drop downward through the beaddrop inlets 805 a-c into a mixing chamber 519 a-c, provided that thecartridge slider 420 is in the correct position.

Reference is now made to FIG. 8B, which depicts a cutaway of thecartridge body 405 including the bead drop inlet 805 a-c, in accordancewith an embodiment. In various embodiments, each mixing chamber 519 a-cincludes a bead drop inlet 805 a-c that extends vertically to the slot440 located above the mixing chamber 519 a-c. The bead drop inlet 805a-c may be located on one side of the mixing chamber 519 a-c; namely,the bead drop inlet 805 a-c is depicted to be on the left side of eachmixing chamber 519 a-c in FIG. 8B. In various embodiments, the height ofeach mixing chamber 519 a-c is designed such that the mixing fluid(e.g., 300 μL total) in the mixing chamber 519 a-c does not escapethrough the slots 440 along the left side of the cartridge body 405.

Reference is now made to FIG. 8C, which depicts a side cutaway of thecartridge body 405 that illustrates the bead drop inlet 805 c inrelation to a mixing chamber 519 c, in accordance with an embodiment. Invarious embodiments, the bead drop inlet 805 a-c is structurallyconfigured to facilitate the entry of a reagent bead into a mixingchamber 519 a-c. For example, as depicted in FIG. 8C, the bottom 810 ofthe bead drop inlet 805 c may be structurally curved such that thereagent bead is directed away from the side of the cartridge body 405into the mixing fluid in the mixing chamber 519 c.

Cartridge Electrode and Cartridge Slider

Reference is now made to FIG. 9A, which depicts a top down view of thecartridge electrodes 425 a-c within the cartridge body 405, inaccordance with an embodiment. Namely, each cartridge electrode 425 a-cis positioned within a slot 440 and extends into a mixing chamber 519a-c. In various embodiments, when cartridge electrodes 425 a-c areinserted into the cartridge body 405, the cartridge electrodes 425 a-csit flush with the left cover 410 of the autoplatelet cartridge 120. Theleft side of the autoplatelet cartridge 120 does not have anyprotrusions, thereby facilitating the process of inserting theautoplatelet cartridge 120 into the analyzer console 140.

The cartridge body 405 may further include multiple loading structures940 a-c, each loading structure 940 a-c adjacent to a correspondingcartridge electrode 425 a-c. As depicted in FIG. 9A, each loadingstructure 940 a-c is to the right of a cartridge electrode 425 a-c. Theloading structures 940 a-c are positioned such that each loadingstructure 940 a-c can receive a reagent bead when the reagent bead isfirst loaded into the assembled autoplatelet cartridge 120. Each loadingstructure 940 a-c prevents the bead from entering into the mixingchamber 519 a-c.

Reference is now made to FIG. 9B-9E, which each depicts a view of acartridge electrode 425 a-c, in accordance with an embodiment. Thecartridge electrode 425 a-c includes a platform 910, a sealing structure915, a sealing face 918, an extension structure 922, one or moreelectrode wires 920 a-b, and one or more contact pads 925 a-b. Furtherdescription regarding the design of cartridge electrodes 425 a-c formeasuring platelet activity is described in U.S. application Ser. No.14/864,634 which is hereby incorporated in its entirety by reference.

The platform 910 of the cartridge electrode 425 a-c serves as astructure that holds a reagent bead prior to being provided to themixing chamber 519 a-c. Namely, the reagent bead sits in contact and ontop of the platform 910. In various embodiments, the platform is ahorizontal structure and is formed from an elastomeric material. Theelastomeric material may be an insulating material. As such, theplatform 905 insulates a reagent bead from temperature differenceswithin the cartridge body 405. As an example, the reagent bead may beheld on the platform 910 while the solution in the mixing chamber 519a-c is mixed and equilibrated (e.g., to 37° C.). Therefore, the platform905 insulates the reagent bead from the heat that may arise from themixing solution that may otherwise adversely affect the activity of thereagent bead.

In various embodiments, when the cartridge electrode 425 a-c is withinthe cartridge body 405, the platform 910 is located immediately adjacentto a corresponding loading structure 940 a-c. As such, the platform 910can receive a reagent bead from the loading structure 940 a-c andsubsequently provide the reagent bead to the mixing chamber 519 a-c. Theprocess of loading a reagent bead into the autoplatelet cartridge 120 isdiscussed in further detail below.

Each cartridge electrode 425 a-c may also include a sealing structure915 that is configured to prevent mixing fluid from leaving the mixingchamber 519 a-c. Namely, the sealing structure 915 serves as astructural barrier located above the mixing chamber 519 a-c. In variousembodiments, the sealing structure 915 is designed to correspond to astructure of the mixing chamber 519 a-c. For example, as previouslystated, the mixing chamber 519 a-c may be cylindrical in shape.Therefore, the sealing structure 915 may be correspondingly designedwith a circular or hemispherical seal to prevent mixing fluid fromleaving the mixing chamber 519 a-c. For example, the sealing structure915 includes a sealing face 918 that is configured to sit in contactwith the walls of the mixing chamber 519 a-c. The sealing face 918 maybe composed of a substance that further prevents fluid from escaping themixing chamber 519 a-c. This includes amounts of evaporated fluid fromthe mixing fluid that may alter the humidity of the microenvironmentaround the platform 910 of the cartridge electrode 425 a-c (e.g., wherethe reagent bead resides). As an example, the sealing face 918 may becoated with a hydrophobic surface coating. As another example, thesealing face 918 may be a rubberized O-ring that enables a strong sealbetween the sealing structure 915 and the walls of the mixing chamber519 a-c.

The extension structure 922 of the cartridge electrode 425 a-c extendsinto the mixing fluid solution within the mixing chamber 519 a-c toenable one or more measurements to be taken by the electrode wires 920a-b. The extension structure 922 vertically extends downward away fromthe body of the cartridge electrode 425 a-c and guides the electrodewires 920 a-b by providing structural integrity to the electrode wires920 a-b. As depicted in FIG. 9B, the extension structure 922 includes acavity 924 such that a portion of the electrode wires 920 a-b can beexposed to the mixing fluid solution without contacting the extensionstructure 922. The extension structure 922 couples with the electrodewires 920 a-b on both sides of the cavity 924.

The electrode wires 920 a-b can be composed of palladium-, silver-, orgold-coated copper or can be pure, uncoated palladium, silver, gold, orcopper. Using palladium-coated copper, for example, can substantiallyreduce the price of manufacture of the electrode assembly. The electrodewires 920 a-b can be attached to the extension structure 922 by glue,adhesive tape, heat staking, welding (e.g., ultrasonic welding), or anyother suitable attachment method that does not damage the electrodewires 920 a-b.

In various embodiments, the electrode wires 920 a-b are positionedperpendicular to a flow of the mixing solution within the mixing chamber519 a-c. As such, the electrode wires 920 a-b can measure impedance orchanges in impedance as the fluid flows perpendicular to the electrodewires 920 a-b. More specifically, as platelet aggregation occurs on theexposed electrode wires 920 a-b, the impedance and change in impedancecan be measured to determine the level of platelet aggregation and/oractivity.

As previously described, the electrode wires 920 a-b are guided alongthe extension structure 922 and may be adhered to the extensionstructure 922 along certain portions of the electrode wire 920 a-b. Asshown in FIG. 9C, which depicts a reverse view of the cartridgeelectrode 425 a-c, each electrode wire 920 a-b can be individuallyattached to a conductive backing 925 a-b such as a copper plate. Namely,as shown in the bottom-up view of the cartridge electrode 425 a-c inFIG. 9D, each electrode wire 920 a-b may be attached to a conductivebacking 925 a-b on the underside of the cartridge electrode 425 a-c.Each conductive backing 925 a-b is distinct (e.g., not in contact) fromanother conductive backing 925 a-b. The analyzer console 140 can measurethe impedance values of each electrode wire 920 a-b by recording ameasurement, such as a voltage reading, at each conductive backing 925a-b.

Referring now to the top down view of the cartridge electrode 425 a-cdepicted in FIG. 9E, the cartridge electrode forms an opening, hereaftertermed the bead drop opening 930. The bead drop opening 930 isconfigured to substantially align with the bead drop inlet 805 a-c ofthe cartridge body 405. As such, a reagent bead can enter into themixing chamber 519 a-c located beneath a cartridge electrode 425 a-c bypassing through the bead drop opening 930 and through the correspondingbead drop inlet 805 a-c.

FIG. 10A depicts a cartridge slider 420, in accordance with anembodiment. As previously described, when the autoplatelet cartridge 120is fully assembled, the cartridge slider 420 is situated within a cavity450 of the cartridge body and is located below the overhang 630 of theleft cover 410 and the overhang 715 of the right cover 415.Additionally, the cartridge slider 420 is located above the cartridgeelectrodes 425 a-c and more specifically, able to slide over theplatforms 910 of the cartridge electrodes 425 a-c.

As depicted in FIG. 10A, the cartridge slider 420 includes one or moreopenings 1010 a-c as well as one or more translational structures 1005a-b. Each opening 1010 a-c may be configured to receive a reagent bead.As shown in FIG. 10A, each opening 1010 a-c is a quadrilateral openingand as such, a spherical reagent bead can readily pass from a top sideof the cartridge slider 420 through to the bottom side of the cartridgeslider 420 by passing through the opening 1010 a-c. In variousembodiments, the cartridge slider 420 may be further structured tofacilitate the entry of a reagent bead into an opening 1010 a-c. Forexample, the walls adjacent to the openings 1010 a-c may be slanted.Therefore, even if a reagent bead is not placed exactly over the opening1010 a-c, the adjacent walls guide the reagent bead to the opening 1010a-c.

The translational structures 1005 a-b are configured to receive input,for example from the analyzer console 140, that causes the cartridgeslider 420 to slide along the cavity 450 of the cartridge body 405. Asan example, a first translational structure 1005 a is located on the topside of the cartridge slider 420. As depicted in FIG. 10A, the firsttranslational structure 1005 a is a cylindrical structure with a hollowinternal cavity. In various embodiments, the first translationalstructure 1005 a is situated below the opening formed by the indentation640 of the left cover 410 and the indentation 740 of the right cover415. Therefore, the analyzer console 140 can apply a physical force(e.g., through a pin or a physical structure) that translates thecartridge slider 420 longitudinally (e.g., to the left or right) alongthe cavity 450 of the cartridge body 405. Additionally, a secondtranslational structure 1005 b on the cartridge slider 420 may beaccessible through slider access port 710 of the right cover 415. Invarious embodiments, the second translational structure 1005 b is a wallof the cartridge slider 420 that is adjacent to a gap. Therefore, theanalyzer console 140 can access the second translational structure 1005b through the slider access port 710 and apply a physical force (e.g.,through a pin or a physical structure) that translates the cartridgeslider 420 longitudinally (e.g., to the left or right) along the cavity450 of the cartridge body 405.

Reference is now made to FIG. 10B, which depicts a side view of thecartridge slider 420, in accordance with an embodiment. As depicted inFIG. 10B, the cartridge slider 420 includes one or more bosses 1020 a-cthat protrude from the surface of the cartridge slider 420. In variousembodiments, the bosses 1020 a-c are located on the cartridge slider 420in order to correspond to the one or more divots 612 a-c (see FIG. 6A)of the left cover. Namely, the height of each boss 1020 a-c correspondsto the depth of the divot 612 a-c. As such, the bosses 1020 a-c can bein contact with the divots 612 a-c in a neutral position (e.g., noforces between the cartridge slider 420 and overhang 630 of the leftcover 410).

The cartridge slider 420 can transition between different positionswithin the cavity 450 to enable loading of reagent beads, holding ofreagent beads, and dropping of reagent beads into the mixing chambers519 a-c. As described hereafter, the various positions will be referredto as the 1) bead loading position, 2) neutral position, 3) bead holdingposition, and 4) bead drop position.

In various embodiments, when the cartridge slider 420 is in the beadloading position, the cartridge slider 420 is in a position that is mostdistal to the sample well 122. Here, the openings 1010 a-c of thecartridge slider 420 are aligned with the overhang openings 625 a-c (seeFIG. 6D) of the overhang 630 of the left cover 410. Therefore, reagentbeads can be provided (e.g., by the analyzer console 140) through theoverhang openings 625 a-c and to the openings 1010 a-c of the cartridgeslider 425 a-c. Additionally, each opening 1010 a-c of the cartridgeslider is aligned with a loading structure 940 a-c of the cartridge body405 (see FIG. 9A). More specifically, each of the loading structures 940a-c obstructs a reagent bead from fully passing through the openings1010 a-c of the cartridge slider 420. As such, when the cartridge slider420 is in the bead loading position, reagent beads can be held withinthe openings 1010 a-c of the cartridge slider 420 in contact with aloading structure 940 a-c of the cartridge body 405. In variousembodiments, to obstruct a reagent bead from passing through an opening1010 a-c of the cartridge slider 420, each loading structure 940 a-c islocated immediately below an opening 1010 a-c of the cartridge slider420. Namely, the distance between the loading structure 940 a-c and thecartridge slider 420 is less than the size of a reagent bead such thatthe reagent bead is held within the opening 1010 a-c of the cartridgeslider 420 by the loading structure 940 a-c.

The cartridge slider 420 may be translated to a neutral position. Invarious embodiments, the cartridge slider 420 is locally more proximalto the sample well 122 when in the neutral position as compared to whenin the bead loading position. In various embodiments, when the cartridgeslider 420 translates from the bead loading position to the neutralposition, the reagent beads held within the openings 1010 a-c of thecartridge slider correspondingly translate along with the cartridgeslider 420.

When in the neutral position, the bosses 1020 a-c of the cartridgeslider correspond to the divots 612 a-c (see FIG. 6A) of the left cover410. As such, the bosses 1020 a-c do not apply pressure to the overhang630 of the left cover 410. Additionally, when the cartridge slider 420is in the neutral position, the cartridge slider 420 serves to block theaccess from the overhang openings 625 a-c to the cartridge electrodes425 a-c and the mixing chambers 519 a-c. Therefore, the cartridge slider420 may be placed in the neutral position when transporting or shippingthe autoplatelet cartridge 120 to ensure stability of substances (e.g.,fluid or magnetic stirrer) within the mixing chamber 519 a-c.

The cartridge slider 420 may also be placed in a bead holding position.In various embodiments, the cartridge slider 420 is locally moreproximal to the sample well 122 when in the bead holding position ascompared to either the neutral position or the bead loading position. Invarious embodiments, when the cartridge slider 420 translates from theneutral position to the bead holding position, the reagent beads heldwithin the openings 1010 a-c of the cartridge slider 420 correspondinglytranslate along with the cartridge slider 420.

When in the bead holding position, each opening 1010 a-c of thecartridge slider 420 is substantially aligned with a platform 910 of acartridge electrode 425 a-c located underneath the cartridge slider 420.As such, a reagent bead can be in contact with a platform 910 whilestill being held within the opening 1010 a-c of the cartridge slider. Invarious embodiments, the distance between the platform 910 of acartridge electrode 425 a-c and the cartridge slider 420 is less thanthe size of a reagent bead such that the reagent bead is held within theopening 1010 a-c of the cartridge slider 420 by the platform 910 of acartridge electrode 425 a-c.

The reagent bead may be held in this position while the mixing solutionin the mixing chamber 519 a-c is equilibrated. While in the bead holdingposition, each opening 1010 a-c of the cartridge slider 420 does notalign with the overhang openings 625 a-c (see FIG. 6D) of the overhang630 of the left cover 410, thereby enabling the reagent bead to remainwithin the autoplatelet cartridge 120 even if the orientation of theautoplatelet cartridge 120 is altered.

The cartridge slider 420 may also be placed in a bead drop position. Invarious embodiments, the cartridge slider 420 is locally more proximalto the sample well 122 when in the bead drop position as compared to anyof the bead holding position, the neutral position, or the bead loadingposition. In various embodiments, when the cartridge slider 420translates from the bead holding position to the bead drop position, thereagent beads held within the openings 1010 a-c of the cartridge slider420 correspondingly translate along with the cartridge slider 420.

When in the bead drop position, each opening 1010 a-c of the cartridgeslider 420 is substantially aligned with the bead drop opening of thecartridge electrode 425 a-c as well as the bead drop inlet 805 a-c ofthe cartridge body 405. As such, when the cartridge slider 420 istranslated to the bead drop position from the bead holding position, areagent bead can be dropped from the platform 910 of the cartridgeelectrode 425 a-c into the mixing chamber 519 a-c.

FIG. 11A-11B each illustrates a cutaway view of an assembledautoplatelet cartridge 120 as a reagent bead enters into a mixingchamber 519 a-c, in accordance with an embodiment. More specifically,FIG. 11A-B each depicts a cutaway view (section L-L) as shown in FIG.8B. FIG. 11A shows the presence of a reagent bead 1110 when thecartridge slider 420 is in the bead holding position. Namely, thereagent bead 1110 is held in contact with the platform 910 of thecartridge electrode 425 a-c. Furthermore, FIG. 11A depicts the sealingstructure 915 of the cartridge 425 a-c which seals the mixing fluidwithin the mixing chamber 522 a. Additionally, the extension structure922 of the cartridge electrode 425 a-c extends into the mixing chamber519 a-c. In various embodiments, the extension structure 922 remains athreshold distance away from the bottom of the mixing chamber 519 a-c.This enables a mixing device to mix the fluid without adverselydisrupting the measurements detected by the electrode wires 920 a-b onthe extension structure 922.

FIG. 11B depicts the position of the reagent bead 1110 immediately afterthe cartridge slider 420 is translated to the bead drop position.Namely, the reagent bead 1110 is dropped into the bead inlet 805 a.Thus, the reagent bead 1110 can be mixed with the fluid within themixing chamber 519 a-c.

The reagent bead may be one of various types of platelet activators. Forexample, a reagent bead may be one or a combination of adenosinediphosphate (ADP), prostaglandin-E1, COX-1, arachidonic acid, Thrombinreceptor-activating peptide (TRAP), and collagen. Although FIGS. 11A and11B were described in reference to one reagent bead, more than onereagent bead may be provided to a mixing chamber 519 a-c fordetermination of platelet activity.

Process of Testing Platelets

FIG. 12A-C illustrates a flow process of testing platelet behavior usingthe autoplatelet cartridge 120, in accordance with an embodiment. Ablood sample 10 can be inserted 1205 into a blood receptacle (e.g.,sample well 122) of the autoplatelet cartridge 120. Here, theautoplatelet cartridge 120 is inserted or may already be inserted into acartridge port 150 of the analyzer console 140. Saline is released 1210into the ampoule chamber 550 of the autoplatelet cartridge 120. In oneembodiment, the saline may be originally housed within the ampoule 408and situated within the ampoule chamber 550. The analyzer console 140may provide an external force through the ampoule access port 545 inorder to release the saline from the ampoule 408. The ampoule chamber550 is then vented 1215 to ensure that air can flow into the ampoulechamber 550 to displace the saline. The ampoule chamber 550 can bevented through vent port 540 located in the ampoule chamber 550.

Saline is flowed 1220 through the fluid channels and into each measuringchamber 518-c of the autoplatelet cartridge 120. To do so, a vacuum canbe applied to the vacuum pressure port 535 that draws the saline throughappropriate fluid channels. Here, the autoplatelet cartridge 120 is inthe following configuration: vent port 540 is open, vent seat 510 isclosed, vent seat 515 is open, vent seat 520 a-c are each closed, ventseat 525 is open, a vacuum is applied to vacuum pressure port 535. Thus,saline can be flowed through fluid channel 560, 564, 566, 568, and 570in filling each measuring chamber 518 a-c. The analyzer console 140 maydetect 1225 that saline has filled each measuring chamber 518 a-c tocapacity. As an example, the analyzer console 140 may detect thepresence of saline at fluid detection location 730 b. Detection ofsaline at fluid detection location 730 b means that saline has filledeach of the measuring chambers 518 a-c.

Saline in each measuring chamber 518 a-c is displaced 1230 into acorresponding mixing chamber 519 a-c. To accomplish this, theautoplatelet cartridge 120 adopts the following configuration: vent port540 is closed, vent seat 510 is closed, vent seat 515 is closed, ventseat 520 a-c are each opened, vent seat 525 is closed, a positivepressure is applied to input pressure port 530. In various embodiments,the saline in each measuring chamber 518 a-c is displaced in sequentialfashion. Namely, a vent seat 520 c is the first among vent seats 520 a-cthat is opened when the positive pressure is applied to input pressureport 530. Thus, saline in measuring chamber 518 c is displaced intomixing chamber 519 c. Subsequently, vent seat 520 c is closed and ventseat 520 b is opened. Thus, saline in measuring chamber 518 b isdisplaced into mixing chamber 519 b. Subsequently, vent seat 520 b isclosed and vent seat 520 a is opened. Thus, saline in measuring chamber518 a is displaced into mixing chamber 519 a. Vent seat 520 a is thenclosed. In various embodiments, the volume of saline displaced into eachmixing chamber 519 a-c is 150 μL. Additionally, a mixing device (e.g.,magnetic stirrer) may rotatably stir the saline in the mixing chamber519 a-c while the analyzer console 140 heats the saline to apredetermined temperature (e.g., 37° C.).

After saline is displaced into each mixing chamber 519 a-c, the salinethat remains within the fluid channels of the autoplatelet cartridge 120is eliminated 1235. To accomplish this, the autoplatelet cartridge 120adopts the following configuration: vent port 540 is open, vent seat 510is closed, vent seat 515 is open, vent seat 520 a-c are each closed,vent seat 525 is open, a vacuum is applied to vacuum pressure port 535.Thus, saline is drawn into waste chamber 590.

After saline is removed from the fluid channels, the blood from theblood sample 10 is flowed 1240 through the fluid channels into each ofthe measuring chambers 518 a-c. Here, the autoplatelet cartridge 120 isin the following configuration: vent port 540 is closed, vent seat 510is open, vent seat 515 is closed, vent seat 520 a-c are each closed,vent seat 525 is open, a vacuum is applied to vacuum pressure port 535.Thus, blood can be flowed through fluid channel 562, 564, 566, 568, and570 in filling each measuring chamber 518 a-c. Similar to the detectionof saline as previously described, the analyzer console 140 may detect1245 that blood has filled each measuring chamber 518 a-c to capacity.As an example, the analyzer console 140 may detect the presence of bloodat fluid detection location 730 b.

The blood in each measuring chamber 518 a-c is displaced 1250 into thecorresponding mixing chamber 519 a-c where the saline is currentlymixing. To accomplish this, the autoplatelet cartridge 120 adopts thefollowing configuration: vent port 540 is closed, vent seat 510 isclosed, vent seat 515 is closed, vent seat 520 a-c are each opened, ventseat 525 is closed, a positive pressure is applied to input pressureport 530. In various embodiments, the blood in each measuring chamber518 a-c is displaced in sequential fashion. Namely, a vent seat 520 c isthe first among vent seats 520 a-c that is opened when the positivepressure is applied to input pressure port 530. Thus, blood in measuringchamber 518 c is displaced into mixing chamber 519 c. Subsequently, ventseat 520 c is closed and vent seat 520 b is opened. Thus, blood inmeasuring chamber 518 b is displaced into mixing chamber 519 b.Subsequently, vent seat 520 b is closed and vent seat 520 a is opened.Thus, blood in measuring chamber 518 a is displaced into mixing chamber519 a. Vent seat 520 a is then closed. In various embodiments, thevolume of blood displaced into each mixing chamber 519 a-c is 150 μL andallowed to mix 1255 with the saline in the mixing chamber 519 a-c. Assuch, the mixture of fluid in the mixing chamber 519 a-c is a 1:1 ratioof blood and saline (e.g., 150 μL of each type of fluid). In variousembodiments, the ratio of the two fluids can be altered and need not beprecisely a 1:1 ratio. Additionally, a mixing device (e.g., magneticstirrer) may rotatably stir the fluid mixture in the mixing chamber 519a-c while the analyzer console 140 heats the mixture to a predeterminedtemperature (e.g., 37° C.).

The remaining blood in the fluid channels of the autoplatelet cartridge120 is eliminated 1260. To accomplish this, the autoplatelet cartridge120 adopts the following configuration: vent port 540 is open, vent seat510 is closed, vent seat 515 is open, vent seat 520 a-c are each closed,vent seat 525 is open, a vacuum is applied to vacuum pressure port 535.Thus, blood is drawn into waste chamber 590.

Although FIGS. 12A and 12B depict a particular flow process, in variousembodiments, the autoplatelet cartridge 120 may first displace bloodinto the mixing chambers 519 a-c (e.g., steps 1240-1260 in FIG. 12B) andsubsequently mix saline into the mixing chambers 519 a-c (e.g., steps1210-1235 in FIG. 12A).

Referring now to FIG. 12C, for each mixing chamber 519 a-c of theautoplatelet cartridge 120, the autoplatelet cartridge 120 receives 1270one or more reagent beads through a cartridge slider 420. As an example,the reagent beads may be inserted through the overhang openings 625 a-cof the left cover 410 into a corresponding opening 1010 a-c of thecartridge slider 420. In various embodiments, the reagent beads areprovided by the analyzer console 140. In other embodiments, the reagentbeads may be pre-loaded into the cartridge slider while the cartridgeslider 420 is in the bead loading position.

The saline and blood mixture is equilibrated 1265. Namely, the analyzerconsole 140 may deem each solution mixture equilibrated if the impedancemeasurement detected by the cartridge electrode 425 a-c (through theelectrode wires 920 a-b) remains within a threshold deviation range fora threshold amount of time. Additionally, the analyzer console 140 mayinclude a temperature sensor that ensures that the temperature of themixing solution in the mixing chamber 519 a-c is also remaining within athreshold deviation range for a threshold amount of time. In variousembodiments, the cartridge slider 420 may be translated to a beadholding position such that the provided reagent beads are held on theplatform 910 of a cartridge electrode 425 a-c while the solution isequilibrated.

Once the mixing solution in each mixing chamber 519 a-c is equilibrated,the one or more reagent beads are provided 1275 to the equilibratedmixture in the mixing chamber 519 a-c. For example, the cartridge slider420 may transition from the bead holding position to the bead dropposition. The cartridge slider 420 may transition in response to anexternal force input provided by the analyzer console 140. In someembodiments, the mixing solution is held for a threshold period of timeto ensure that the reagent bead fully dissolves within the mixingchamber 519 a-c.

After adding the reagent beads, the analyzer console 140 may measure1280 impedance changes within the mixture due to the provided one ormore reagent beads. In various embodiments, each mixing chamber isprovided a different reagent bead that provides a different measurableof platelet activity. For example, the reagent bead may cause plateletaggregation on the electrode wires 920 a-c of the cartridge electrode425 a-c. As such, the analyzer console 140 may determine 1285 plateletactivity of the blood sample based on the measured impedance changes.

Computing System

FIG. 13A-B illustrate an overview of the analyzer console 140, inaccordance with an embodiment. Referring to FIG. 13a , the main chassis144 of the analyzer console 140 can include a front portion 144 f and arear portion 144 b. In some embodiments, the rear portion 144 b housesat least some of the computer and electronic components that arenecessary for the operations of the analyzer console 140. For example,the rear portion 144 b can house hardware devices and software such as,but not limited to, computer processors, memory devices, an operatingsystem and other executable instructions, power source(s), userinterface controls, communication devices, circuit boards, and the like.

In the depicted embodiment, the front portion 144 f includes a cover1345 and a sample handler assembly 1300. The sample handler assembly1300 defines an interior space in which the cartridge 120 can bereceived. In some embodiments, the sample handler assembly 1300 is amodular sub-assembly of the analyzer console 140, and the sample handlerassembly 1300 can be readily removed from the analyzer console 140 forservice. The sample handler assembly 1300 is electrically interconnectedwith the computer and electronic components that are housed in the rearportion 144 b. As such, the analyzer console 140 can perform testing ona blood sample located in cartridge 120 and display the results on thetouchscreen display 142.

Referring now to FIG. 13B, the analyzer console 140 can include acartridge receiver and clamp 1310 and a platelet activity measurementsystem 1380. A mechanical frame assembly is used to support thecartridge receiver and clamp 1310 and the platelet activity measurementsystem 1380 in orientations such that the cartridge receiver and clamp1310 and the viscoelastic measurement system 1380 can functionsymbiotically.

Portions of the cartridge receiver and clamp 1310 and the plateletactivity measurement system 1380 are moveable in relation to themechanical frame assembly (which is stationary in relation to theanalyzer console 140). For example, the platelet activity measurementsystem 1380 can move upward and downward. As will be described furtherbelow, the platelet activity measurement system 1380 can move downwardto engage with the cartridge 120 (e.g., refer to FIG. 13A), and upwardto disengage from the cartridge 120. A portion of the cartridge receiverand clamp 1310 can move horizontally in relation to the mechanical frameassembly. As will be described further below, a portion of the cartridgereceiver and clamp 1310 can move horizontally to clamp or unclamp thecartridge 120 within the sample handler assembly 1300.

In some embodiments, the cartridge receiver and clamp 1310 includes amovable block sub-assembly and a stationary block sub-assembly. A spaceexists between the movable block sub-assembly and the stationary blocksub-assembly in which the cartridge 120 can be received. The movableblock sub-assembly can be translated towards or away from the stationaryblock sub-assembly. Accordingly, the cartridge 120 can be clamped andunclamped between the movable block sub-assembly and the stationaryblock sub-assembly by virtue of the relative movement therebetween. Insome embodiments, the platelet activity measurement system 1380 ismounted to the movable block sub-assembly. Therefore, as the movableblock sub-assembly is translated, the platelet activity measurementsystem 1380 is also translated.

In some embodiments, the moveable block sub-assembly can be translatedby an electric motor. In particular embodiments, the motor is a steppermotor. In some embodiments, a gear reducer is coupled to the motor.Using a belt and pulley arrangement for compactness, the motor can beused to drive a lead screw. The threads of the lead screw can be engagedwith complementary threads of the movable block such that a rotation ofthe lead screw results in horizontal translation of the movable block.In some embodiments, end-of-travel detectors (e.g., proximity sensors,optical sensors, micro-switches, and the like) are included to detectwhen the moveable block sub-assembly has been horizontally translated tothe desired end-of-travel positions.

In some embodiments, one or more springs can extend between the movablemoveable block sub-assembly and the stationary block sub-assembly. Thesprings can help facilitate a suitable clamping force between themovable block sub-assembly and the stationary block sub-assembly. Insome embodiments, the springs are adjustable.

In some embodiments, portions of the moveable block sub-assembly and thestationary block sub-assembly that make contact with the cartridge 120comprise a flexible or compressible material so that while the cartridge120 is clamped it is also protected from damage.

In some embodiments, one or both of the moveable block sub-assembly andthe stationary block sub-assembly include heating devices 1312 that canwarm the cartridge 120 when the cartridge 120 is clamped therebetween.For example, in some embodiments the heaters 1312 are electricalresistance heaters that are used to heat at least portions (e.g., mixingchamber 519 a-c) of the cartridge 120 to a predesignated temperature(e.g., 37°). In some embodiments, the heaters 1312 are configured tofacilitate warming of individual portions of the cartridge 120independently from other portions of the cartridge 120. For example, oneor more of the individual fluid channels 560, 562, 564, 566, 568, 570,572, and 580 a-c (see FIG. 5A) can be independently warmed in some suchembodiments. Warming may be performed to one or more sides of thecartridge 120. Other types of warming modalities may be used including,but not limited to, IR, ultrasonic, microwave, and the like.

In particular embodiments, one or more temperature sensors 1314 areincluded that can detect the temperature of the cartridge 120 at one ormore locations on the cartridge 120. For example, in some embodimentsthe one or more temperature sensors 1314 can be thermocouples,thermistors, infra-red temperature sensors, and the like. Accordingly,the analyzer console 140 can control the heating of the cartridge 120 toa predetermined temperature (e.g., about 37° C.) using the heaters 1312and the temperature sensors 1314.

The moveable block sub-assembly can include multiple solenoids that areused to actuate the aforementioned vents and valves of the cartridge120. For example the valve structures 605 a-f can be actuated by valveactuators 1330 and the vent port 540 can be actuated by vent actuators1332. In some embodiments, the valve actuators 1330 and the ventactuators 1332 comprise solenoids. Actuation of the valve structures 605a-f by the valve actuators 1330 can be accomplished by coupling pins tothe valve actuators 1330 that are extendable from the moveable blocksub-assembly to make contact with and to distend valve elastomer membersso that the elastomer members make contact with a valve seat within thecartridge 120. Actuation of the vent port 540 by the vent actuators 1332can be accomplished by coupling pins with resilient tips that areextendable from the moveable block sub-assembly to obstruct the ventport 540. Such pins with resilient tips can act as stoppers tosubstantially prevent airflow through the vent port 540. In someembodiments, the valve actuators 1330 and the vent actuators 1332comprise solenoids that include internal springs that cause the valveactuators 1330 and the vent actuators 1332 to be normally extended(e.g., when the electrical power is removed from the solenoids).Accordingly, such normally closed solenoids will close the vents andvalves of the cartridge 120 as a default configuration.

The sample handler assembly 1300 also includes pressure source 1336 andvacuum source 1334 by which air pressure and vacuum can be applied tothe input pressure port 530 and vacuum pressure port 535 of autoplateletcartridge 120 respectively. For example, the pressure source 1336 andvacuum source 1334 can make contact with the cartridge 120 and canconvey pressure or vacuum to the input pressure port 530 and vacuumpressure port 535 when the cartridge 120 is clamped within the cartridgereceiver and clamp 1310. The pressure source 1336 and vacuum source 1334are at least partially made of a resilient material in some embodiments.For example, in some embodiments the pressure source 1336 and vacuumsource 1334 are at least partially made of a resilient material such as,but not limited to, silicone, butyl rubber, nitrile rubber, ethylenepropylene rubber, fluoroelastomers, and the like. One or moreinternally-housed pressure and/or vacuum pumps (not shown) can also beincluded in the analyzer console 140. Such internally-housed pressureand vacuum pumps can be used to generate the air pressure or vacuum thatis applied to the cartridge 120 to induce the transport of fluid withinthe autoplatelet cartridge 120 as described above.

As previously described, the cartridge receiver and clamp 1310 alsoincludes the stationary block sub-assembly. In some embodiments, thestationary block sub-assembly does not move in relation to themechanical frame assembly and in relation to the analyzer console 140 asa whole.

In some embodiments, the analyzer console 140 includes a mixing unit1340. In particular embodiments, the mixing unit 1340 includes a motor,a crank and connecting rod assembly, and a magnet shuttle. Thesecomponents can be used to magnetically couple with the mixing elements(e.g., magnetic stirrer) of the autoplatelet cartridge 120 and to inducemovement of the mixing elements within the mixing chambers 519 a-c. Themovement of the mixing elements encourages the reagent beads to dissolvein the mixing fluid contained within the mixing chambers 519 a-c asdescribed above.

The analyzer console 140 can also include one or more sensors 1348. Theone or more sensors 1348 can be used to detect the presence of fluid inparticular locations within the cartridge 120, such as fluid detectionlocations 127 a and 730 a-b as described above. In some embodiments, thesensors 1348 are optical sensors, such as IR (infrared) sensors. In someembodiments, the sensors 1348 can be used to detect fluid in other areasof the cartridge 120.

The sample handler assembly 1300 of the analyzer console 140 alsoincludes the platelet activity measurement system 1380. In variousembodiments, the platelet activity measurement system 1380 may includeone or more assemblies that provides a physical input to the ampoule 408within the autoplatelet cartridge 120 through ampoule access port 545.As an example, the physical input may be provided by a structure thatextends through the ampoule access port 545 and physically impacts theampoule 408. As another example, the physical input may be analternative means of energy such as an ultrasound application. Theplatelet activity measurement system 1380 may further include one ormore assemblies that include a structure that provides a physical inputto the translational structures 1005 a-b of the cartridge slider 420 inorder to translate the cartridge slider 420 to various positions. Theplatelet activity measurement system 1380 may further include variouswire leads that are configured to contact the contact pads 925 a-b ofeach cartridge electrode 425 a-c in order to obtain the impedancemeasurement detected by the corresponding electrode wires 920 a-b.

In addition to the aforementioned features of the analyzer console 140,in some embodiments the analyzer console 140 also includes one or moreof the following features. The analyzer console 140 can include one ormore barcode scanners 1350 that, for example, can read a barcode on theautoplate cartridge 120. In some embodiments, the analyzer console 140can include one or more devices to detect the presence of the cartridge120 in a desired insertion location and/or orientation. For example, insome embodiments one or more micro switches can be used to detect whenthe cartridge 120 has been inserted in a desired location andorientation within the sample handler assembly 1300. In someembodiments, the analyzer console 140 can include one or more auxiliaryconnections 1360. The auxiliary connections 1360 can include network anddevice connectors such as, but not limited to, one or more USB ports,Ethernet ports (e.g., RJ45), VGA connectors, Sub-D9 connectors (RS232),and the like. Such auxiliary connections 1360 can be located on the rearof the main chassis 144, or at other convenient locations on the mainchassis 144. For example, in some embodiments one or more USB ports maybe located on or near the front of the main chassis 144.

The analyzer console 140 also includes a user interface 142 (e.g., witha touchscreen display in this embodiment). In the depicted embodiment,the user interface 142 is configured to receive user input and todisplay output information to the user. For example, the user can enterinformation to the analyzer console 140 by making selections of varioussoft-buttons that may be displayed on the user interface 142 at timesduring the beginning, middle, and end of the testing process. In someembodiments, other selections such as, but not limited to, soft keyboardentries can be provided via user interface 142. In some embodiments,data entry can be performed additionally or alternatively by voiceentry. In some embodiments, the user interface may include otherperipheral devices (e.g., a mouse, a keyboard, an additional displaydevice, and the like) as part of the analyzer console 140. In someembodiments, a computer data network (e.g., intranet, internet, LAN,etc.) may be used to allow for remote devices to receive and/or inputinformation from the system 100. For example, in some embodiments one ormore remote displays can be utilized via auxiliary connections 1360. Inthe depicted embodiment, the user interface 142 also includes anexternal barcode reader. Alternatively or additionally, the userinterface 142 of the analyzer console 140 can be equipped with a readerconfigured to read near-field communication tags, RFID tags, or thelike. The analyzer console 140 can also include one or more controlsystems 1370 that can execute instructions embodied in a computerprogram. The control systems 1370 can include, by way of example, bothgeneral and special purpose microprocessors, and any one or moreprocessors of any kind of digital computer. In some embodiments, thecontrol systems 1370 includes one or more such processors, memory,storage devices, interfaces, and other types of electronic sub-systemsand components. Such components may be mounted on a common motherboardor in other manners as appropriate. The control systems 1370 can processinstructions for execution within the analyzer console 140, includinginstructions stored in the memory or on the storage device. In someimplementations, multiple processors and/or multiple buses may be used,as appropriate, along with multiple memories and types of memory. Also,multiple computing devices may be connected, with each device providingportions of the necessary operations (e.g., as a server bank, a group ofblade servers, or a multi-processor system).

The storage devices are capable of providing mass storage for thecontrol systems 1370. In some implementations, the storage device may beor contain a computer-readable medium, such as a floppy disk device, ahard disk device, an optical disk device, or a tape device, a flashmemory or other similar solid state memory device, or an array ofdevices, including devices in a storage area network or otherconfigurations. A computer program product can be tangibly embodied inan information carrier. The computer program product may also containinstructions that, when executed, perform one or more methods, such asthose described above. The computer program product can also be tangiblyembodied in a computer- or machine-readable medium, such as the memory,the storage device, or memory on the processor(s).

Additional Embodiment Considerations

Throughout this specification, as used herein, the terms “comprises,”“comprising,” “includes,” “including,” “has,” “having” or any othervariation thereof, are intended to cover a non-exclusive inclusion. Forexample, a process, method, article, or apparatus that comprises a listof elements is not necessarily limited to only those elements but mayinclude other elements not expressly listed or inherent to such process,method, article, or apparatus.

In addition, use of the “a” or “an” are employed to describe elementsand components of the embodiments herein. This is done merely forconvenience and to give a general sense of the invention. Thisdescription should be read to include one or at least one and thesingular also includes the plural unless it is obvious that it is meantotherwise.

Finally, as used herein any reference to “one embodiment,” “someembodiments,” or “various embodiments” means that a particular element,feature, structure, or characteristic described in connection with theembodiment is included in at least one embodiment. The appearances ofthe phrase “in one embodiment” in various places in the specificationare not necessarily all referring to the same embodiment.

Upon reading this disclosure, those of skilled in the art willappreciate still additional alternative structural and functionaldesigns for propeller blades as disclosed from the principles herein.Thus, while particular embodiments and applications have beenillustrated and described, it is to be understood that the disclosedembodiments are not limited to the precise construction and componentsdisclosed herein. Various modifications, changes and variations, whichwill be apparent to those skilled in the art, may be made in thearrangement and details of the apparatus disclosed herein withoutdeparting from the spirit and scope defined in the appended claims.

What is claimed is:
 1. A cartridge device for testing platelet activityin a blood sample comprising: a cartridge body comprising: a measuringchamber configured to contain a defined volume of fluid; a mixingchamber in fluid communication with the measuring chamber through a ductthat further comprises a valve seat, the mixing chamber furthercomprising an inlet for receiving a reagent bead; and a cavity locatedon a top surface of the cartridge body; a left cover coupled to thecartridge body, the left cover comprising: a valve structure configuredto couple with the valve seat of the cartridge body and block fluid flowbetween the measuring chamber and mixing chamber; a cartridge slidercomprising an opening configured to receive the reagent bead, thecartridge slider located within the cavity of the cartridge body; and acartridge electrode configured to couple with the cartridge body, thecartridge electrode comprising: an extension structure; and one or moreelectrode wires coupled to the extension structure, wherein a portion ofthe one or more electrode wires are situated within the mixing chamberof the cartridge body when the cartridge electrode is coupled with thecartridge body.
 2. The cartridge device of claim 1 further comprising: aright cover coupled to the cartridge body, the right cover comprisingone or more access ports enabling access to the cartridge slider.
 3. Thecartridge device of claim 1, wherein the left cover further comprises: abead opening on a top surface of the left cover, the bead openingaligned with the inlet of the mixing chamber.
 4. The cartridge device ofclaim 1, wherein the valve structure comprises an elastomeric member. 5.The cartridge device of claim 4, wherein the elastomeric material of thevalve structure deforms in response to an external input to couple withthe valve seat of the cartridge body.
 6. The cartridge device of claim1, wherein the cartridge body further comprises: an ampoule chamber thatfurther comprises a hermetically sealed container, wherein the ampoulechamber is in fluid communication with the measuring chamber through afluid channel.
 7. The cartridge device of claim 6, wherein the cartridgebody further comprises an access port that is configured to receive anexternal input, wherein the external input causes the hermeticallysealed container to release a fluid into the ampoule chamber.
 8. Thecartridge device of claim 6, wherein the cartridge body furthercomprises: a sample well configured to receive a blood sample; a secondvalve seat located between the ampoule chamber and the fluid channel,wherein the second valve seat, when open, enables fluid flow between theampoule chamber and the fluid channel; and a third valve seat locatedbetween the sample well and the fluid channel, wherein the third valveseat, when open, enables fluid flow between the sample well and thefluid channel.
 9. The cartridge device of claim 1, wherein the cartridgebody further comprises: a second measuring chamber configured to containa second defined volume of fluid; and a third measuring chamberconfigured to contain a third defined volume of fluid, wherein the thirdmeasuring chamber is in fluid communication with the second measuringchamber, and wherein the second measuring chamber is in fluidcommunication with the measuring chamber.
 10. The cartridge device ofclaim 1, wherein the cartridge electrode further comprises: a platformcomprising an elastomer material surface; and a sealing structureconfigured to seal a fluid within the mixing chamber of the cartridgebody.
 11. The cartridge device of claim 10, wherein the cartridgeelectrode further comprises: an opening adjacent to the platform,wherein the opening of the cartridge electrode is aligned with the inletof the mixing chamber of the cartridge body.
 12. The cartridge device ofclaim 10, wherein the sealing structure comprises a sealing surface thatis one of a rubber O-ring or a hydrophobic surface coating.
 13. Thecartridge device of claim 1, wherein the cartridge body furthercomprises a loading structure, and wherein the opening of the cartridgeslider is aligned with the loading structure of the cartridge body whenthe cartridge slider is in a first position.
 14. The cartridge device ofclaim 1, wherein the cartridge slider further comprises a boss elevatedfrom a surface of the cartridge slider, the boss configured to couplewith a divot on the left cover when the cartridge slider is in a secondposition.
 15. The cartridge device of claim 1, wherein the opening ofthe cartridge slider is aligned with a platform of the cartridgeelectrode when the cartridge slider is in a third position.
 16. Thecartridge device of claim 1, wherein the opening of the cartridge slideris aligned with the inlet of the mixing chamber of the cartridge bodywhen the cartridge slider is in a fourth position.
 17. A method oftesting platelet activity in a blood sample using the cartridge deviceof claim 1, the method comprising: flowing a first fluid into themeasuring chamber; displacing the first fluid from the measuring chamberinto the mixing chamber; flowing a second fluid into the measuringchamber; displacing the second fluid from the measuring chamber into themixing chamber to mix with the first fluid; translating the cartridgeslider to a position within the cavity of the cartridge body to providea reagent bead to the mixing chamber; and determining platelet activityof the blood sample based on measurements taken from a mixture of thefirst and second fluids in the mixing chamber by the cartridge electrodeof the cartridge device.
 18. The method of claim 17, wherein the firstfluid is saline and the second fluid is a portion of the blood sample.19. The method of claim 17, wherein the first fluid and second fluid aremixed in the mixing chamber at equal volumes.
 20. The method of claim17, wherein the measurements taken by the cartridge electrode compriseimpedance changes over time.
 21. A cartridge device for testing plateletactivity in a blood sample comprising: a cartridge body comprising: ameasuring chamber configured to contain a defined volume of fluid; and amixing chamber in fluid communication with the measuring chamber througha duct that further comprises a valve seat, the valve seat configured toprevent fluid flow from the measuring chamber to the mixing chamber whencoupled with a valve structure; a cartridge electrode configured tocouple with the cartridge body, wherein a portion of the cartridgeelectrode is situated within the mixing chamber of the cartridge bodywhen the cartridge electrode is coupled with the cartridge body.
 22. Thecartridge device of claim 21, wherein the cartridge body furthercomprises: a second measuring chamber configured to contain a seconddefined volume of fluid; and a third measuring chamber configured tocontain a third defined volume of fluid, wherein the third measuringchamber is in fluid communication with the second measuring chamber, andwherein the second measuring chamber is in fluid communication with themeasuring chamber.
 23. The cartridge device of claim 21, wherein thecartridge electrode further comprises: a platform comprising anelastomer material surface; and a sealing structure configured to sealfluid within the mixing chamber of the cartridge body.
 24. The cartridgedevice of claim 23, wherein the cartridge electrode further comprises:an opening adjacent to the platform, wherein the opening of thecartridge electrode is aligned with an inlet of the mixing chamber ofthe cartridge body.
 25. The cartridge device of claim 23, wherein thesealing structure comprises a sealing surface that is one of a rubberO-ring or a hydrophobic surface coating.
 26. The cartridge device ofclaim 21, wherein the cartridge body further comprises: an ampoulechamber that comprises a hermetically sealed container, wherein theampoule chamber is in fluid communication with the measuring chamberthrough a fluid channel.
 27. The cartridge device of claim 26, whereinthe cartridge body further comprises an access port that is configuredto receive an external input, wherein the external input causes thehermetically sealed container to release a fluid into the ampoulechamber.
 28. The cartridge device of claim 21 further comprising: acartridge slider comprising an opening configured to receive a reagentbead, the cartridge slider further configured to provide the receivedreagent bead to an inlet of the mixing chamber of the cartridge body.